DESCRIPTION: (provided by the applicant) Nearly 90 percent of all smokers begin smoking during adolescence and about 3,000 adolescents start smoking every day in the United States. The likelihood of quitting smoking in adulthood is decreased dramatically when smoking initiation begins during adolescence. In fact, adolescents who start smoking today will smoke for as long as 20-30 years, on average, which also means that they are more likely to experience the adverse health consequences of smoking than are those individuals who start to smoke later in life. Despite these staggering statistics that suggest a developmental vulnerability to nicotine, little is known about the progression from adolescent experimentation with cigarettes into smoking addiction. Adolescent exposure to nicotine through cigarette smoking also appears to mark the first stage of additional addictive drug involvement in vulnerable individuals. One hypothesis consistent with these epidemiologic data is that the direct pharmacological actions of nicotine in adolescence may influence the vulnerability to consume addictive drugs, including nicotine, in adulthood. To the extent that animal models predict self-administration of addictive substances in adults, they also could be used to understand why adolescent humans begin to smoke, and how smoking might increase the propensity to consume addictive drugs in some individuals. Unfortunately, behavioral animal models of adolescent drug self-administration are rare, particularly with respect to nicotine, the primary addictive ingredient in cigarettes. Therefore, the present proposal will examine the preference for nicotine in periadolescent mice given access to differences doses of nicotine. In addition, nicotine preference will be tested in adult mice following an opportunity to consume nicotine in the adolescent developmental period. Results from this work will set the stage for future research to characterize behavioral (drug self-administration) and biological (molecular, genetic, neuroendocrine) alterations that occur following adolescent exposure to nicotine and to aid in future development of therapies for smoking - the single most preventable cause of death in the United States.